Transcutaneous ultrasound-mediated destruction (UMD) of microbubbles could potentially be utilized in cardiovascular therapy. The central hypothesis of this project is that UMD of microbubbles can noninvasively (1) target delivery of antisense oligonucleotides, and (2) produce arterial thrombus microfragmentation. Since perfluorocarbon containing dextrose albumin microbubbles (PCMB) have the ability to bind antisense oligonucleotides, UMD of intravenously injected synthetic antisense oliogonucleotides bound to PCMB will be utilized to target their disposition to the myocardium and vascular wall. Subsequent to this, the applicants proposed to examine the potential for intravenous antisense to the protooncogene c-myc bound to PCMB to inhibit neointimal hyperplasia following balloon injury in an animal model. Secondly, the potential for UMD of intravenous PCMB to fragment acute coronary and carotid artery thrombi in the absence of a thrombolytic agent in an animal model will be tested. This three year project will therefore test the ability of UMD of PCMB to non-invasively (a) target gene delivery to the vascular wall, and (b) recanalize coronary and carotid thrombotic occlusions without thrombolytic therapy. Phase III studies will then test the effectiveness of antisense delivery in preventing restenosis following percutaneous revascularization procedures in humans and to improve reperfusion success rates in acute myocardial infarction. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE